The two goals of this Bioengineering Research Partnership are (1) to design and construct a new generation of instruments for noninvasive imaging of the mammalian retina with 3-D resolution superior to existing technology and capable of resolving single cells in vivo. (2) to explore the value of this technology through application to human retinal disease and retinal surgery. These instruments will combine adaptive optics, a technology borrowed from astronomy that automatically corrects all the eye's aberrations, with confocal microscopy, a technology for optically sectioning the retina. The lead institution will be the University of Rochester, and partners include Lawrence Livermore National Laboratory, the Doheny Eye Institute at USC, the University of Houston, the University of California at Berkeley, and the Schepens Eye Research Institute. By the end of year 1, a device will be operational at each of four clinical sites: USC, Rochester, Houston, and Schepens. In years 2-5, these devices will provide high resolution imaging of neovascularization in age related macular degeneration and diabetic retinopathy, photoreceptors in retinal degenerative disease such as retinitis pigmentosa, ganglion cell bodies in glaucoma, individual retinal pigment epithelial cells, and blood flow in the smallest retinal capilliaries. In year 3, a new surgical microscope equipped with adaptive optics will be constructed by LLNL. Retinal surgeons at USC will evaluate this device in years 4-5. Based on its experience with earlier instruments, the BRP will design and build a sixth instrument in year 4 that will be portable, compact, and user friendly. This device will be available to investigators outside the BRP. The BRP brings together optical engineers, basic vision scientists, and clinical vision researchers. This will allow engineers to design instrumentation informed by the specific needs of clinical research, allowing them to translate adaptive optics technology directly into clinical application. LLNL brings to the partnership expertise in optical engineering and adaptive optics from the fields of astronomy and laser fusion. Rochester and Houston will contribute experience in adaptive optics applied to retinal imaging. Rochester first applied adaptive optics to high resolution retinal imaging and Houston has recently demonstrated a prototype adaptive optics system that is the precursor for the devices proposed here. Schepens brings international leadership in scanning laser ophthalmoscopy. UC Berkeley provides expertise in the study of retinal degenerative diseases. USC, with its innovative approaches to retinal disease and retinal surgery, will join Rochester, Houston, and Schepens in providing clinical sites for the evaluation of confocal adaptive optics technology.